Risk factors for COVID-19 among healthcare workers. A protocol for a systematic review and meta-analysis

Evidence on the spectrum of risk factors for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among front-line healthcare workers (HCWs) has not been well-described. While several studies evaluating the risk factors associated with SARS-CoV-2 infection among patient-facing and non-patient-facing front-line HCWs have been reported since the outbreak of the coronavirus disease in 2019 (COVID-19), and several more are still underway. There is, therefore, an immediate need for an ongoing, rigorous systematic review that continuously assesses the risk factors of SARS-CoV-2 infection among front-line HCWs.Here, we outline a protocol to serve as a guideline for conducting a living systematic review and meta-analysis to examine the burden of COVID-19 on front-line HCWs and identify risk factors for SARS-CoV-2 infection in patient-facing and non-patient-facing front-line HCWs

COVID-19 prevalence among healthcare workers. A systematic review and meta-analysis

Understanding the burden of SARS-CoV-2 infections among healthcare workers is a critical component to inform occupational health policy and strategy. We conducted a systematic review and meta-analysis to map and analayse the available global evidence on the prevalence of SARS-CoV-2 infections among healthcare workers. The random-effects adjusted pooled prevalence of COVID-19 among those studies that conducted the test using the antibody (Ab) method was 7% [95% CI: 3 to 17%]. The random-effects adjusted pooled prevalence of COVID-19 among those studies that conducted the test using the PCR method was 11% [95% CI: 7 to 16%]. We found the burden of COVID-19 among healthcare workers to be quite significant and therefore a cause for global health concern. Furthermore, COVID-19 infections among healthcare workers affect service delivery through workers’ sick leave, the isolation of confirmed cases and quarantine of contacts, all of which place significant strain on an already shrunken health workforce.SUPPLEMENTARY MATERIALS : SUPPLEMENTARY FILE S1: PRISMA Flow Diagram, SUPPLEMENTARY FILE S2: List of full text articles reviewed, SUPPLEMENTARY FILE S3: Distribution of COVID-19 burden among health care workers in included studies, SUPPLEMENTARY FILE S4: Characteristics of included studies, SUPPLEMENTARY FILE S5: Egger’s plots for assessing the presence of publication bias for the meta-analysis, SUPPLEMENTARY FILE S6: Presentation of findings for assessing and accounting for small-study effects.https://www.mdpi.com/journal/ijerphSchool of Health Systems and Public Health (SHSPH

Risk factors for COVID-19 infection among healthcare workers. A first report from a living systematic review and meta-analysis

Health care workers (HCWs) are more than ten times more likely to be infected with coronavirus infectious disease 2019 (COVID-19) than the general population, thus demonstrating the burden of COVID- 19 among HCWs. Factors that expose HCWs to a differentially high-risk of COVID-19 acquisition are important to elucidate, enable appropriate public health interventions to mitigate against high risk and reduce adverse outcomes from the infection. We conducted a systematic review and meta-analysis to summarize and critically analyze the existing evidence on SARS-CoV-2 risk factors among HCWs. With no geographical limitation, we included studies, in any country, that reported (i) the PCR laboratory diagnosis of COVID-19 as an independent variable (ii) one or more COVID-19 risk factors among HCWs with risk estimates (relative risk, odds ratio, or hazard ratio) (iii) original, quantitative study design, and published in English or Mandarian. Our initial search resulted in 470 articles overall, however, only 10 studies met the inclusion criteria for this review. Out of the 10 studies included in the review, inadequate/ lack of protective personal equipment, performing tracheal intubation, and gender were the most common risk factors of COVID-19. Based on the random effects adjusted pooled relative risk, HCWs who reported the use of protective personal equipment were 29% (95% CI: 16% to 41%) less likely to test positive for COVID-19. The study also revealed that HCWs who performed tracheal intubations were 34% (95% CI: 14% to 57%) more likely to test positive for COVID-19. Interestingly, this study showed that female HCWs are at 11% higher risk (RR 1.11 95% CI 1.01e1.21) of COVID-19 than their male counterparts. This article presents initial findings from a living systematic review and meta-analysis, therefore, did not yield many studies; however, it revealed a significant insight into better understanding COVID-19 risk factors among HCWs; insights important for devising preventive strategies that protect them from this infection.http://www.e-shaw.netam2023School of Health Systems and Public Health (SHSPH

Risk factors for COVID-19 infection among healthcare workers. A first report from a living systematic review and meta-analysis

Health care workers (HCWs) are more than ten times more likely to be infected with COVID-19 compared to the general population, thus demonstrating the burden of COVID-19 among HCWs. Factors that expose HCWs to a differentially high-risk of COVID-19 acquisition are important to elucidate, to enable appropriate public health interventions to mitigate against high risk and reduce adverse outcomes from the infection. We conducted a systematic review and meta analysis to summarise and critically analyse the existing evidence on SARS-CoV-2 risk factors among HCWs. With no geographical limitation, we included studies, in any country, that reported (i) PCR laboratory diagnosis of COVID—19 as an independent variable (ii) one or more COVID-19 risk factors among health care workers with risk estimates (relative risk, odds ratio or harzard ratio) (iii) original, quantitative study design and published in English or Mandarian. Our initial search resulted in 470 articles overall, however, only 10 studies met the inclusion criteria for this review. Out of the 10 studies included in the review, inadequate/lack of protective personal equipment (PPE), performing tracheal intubation (PTI) and gender were the most common risk factors of COVID-19. Based on the random effects adjusted pooled relative risk, HCWs who reported use PPE were 29% (95% CI: 16% to 41%) less likely to test positive for COVID-19. The study also revealed that HCWs who performed tracheal intubations were 34% (95% CI: 14% to 57%) more likely to test positive for COVID-19. Interestingly, this study showed that female HCWs are at 11% higher risk (RR 1.11 95% CI 1.01-1.21) of COVID-19 than their male counterparts. This paper presents initial findings from a living systematic review and meta-analysis, therefore, did not yield many studies, however, it revealed a significant insight to better understand COVID-19 risk factors among HCWs; insights important for devising preventive strategies that protect them from this infection

ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing.

BACKGROUND: Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children < 14 kg while dosing was in development. METHODS: ODYSSEY (Once-daily DTG based ART in Young people vS. Standard thErapY) is an open-label, randomised, non-inferiority, basket trial comparing the efficacy and safety of DTG + 2 nucleos(t) ides (NRTIs) versus standard-of-care (SOC) in HIV-infected children < 18 years starting first-line ART (ODYSSEY A) or switching to second-line ART (ODYSSEY B). The primary endpoint is clinical or virological failure by 96 weeks. RESULTS: Between September 2016 and June 2018, 707 children weighing ≥14 kg were enrolled; including 311 ART-naïve children and 396 children starting second-line. 47% of children were enrolled in Uganda, 21% Zimbabwe, 20% South Africa, 9% Thailand, 4% Europe. 362 (51%) participants were male; median age [range] at enrolment was 12.2 years [2.9-18.0]. 82 (12%) children weighed 14 to < 20 kg, 135 (19%) 20 to < 25 kg, 206 (29%) 25 to < 35 kg, 284 (40%) ≥35 kg. 128 (18%) had WHO stage 3 and 60 (8%) WHO stage 4 disease. Challenges encountered include: (i) running the trial across high- to low-income countries with differing frequencies of standard-of-care viral load monitoring; (ii) evaluating pragmatic DTG dosing in PK sub-studies alongside FDA- and EMA-approved dosing and subsequently transitioning participants to new recommended doses; (iii) delays in dosing information for children weighing 3 to < 14 kg and rapid recruitment of ART-naïve older/heavier children, which led to capping recruitment of participants weighing ≥35 kg in ODYSSEY A and extending recruitment (above 700) to allow for ≥60 additional children weighing between 3 to < 14 kg with associated PK; (iv) a safety alert associated with DTG use during pregnancy, which required a review of the safety plan for adolescent girls. CONCLUSIONS: By employing a basket design, to include ART-naïve and -experienced children, and nested PK sub-studies, the ODYSSEY trial efficiently evaluates multiple scientific questions regarding dosing and effectiveness of DTG-based ART in children. TRIAL REGISTRATION: NCT, NCT02259127 , registered 7th October 2014; EUDRACT, 2014-002632-14, registered 18th June 2014 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002632-14/ES ); ISRCTN, ISRCTN91737921 , registered 4th October 2014

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial.

This article has been accepted for publication in Clinical Infectious Diseases Published by Oxford University PressBackground: Severely immunocompromised human immunodeficiency virus (HIV)-infected individuals have high mortality shortly after starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods: The Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children ≥5 years of age with CD4 counts .1). Results: Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P < .04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P = .02). Of five late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/µL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/µL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/µL), but low symptom burden and maintained fat mass. The remaining groups had 4%-6% mortality. Conclusions: Clinical and laboratory features identified groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up. Clinical Trials Registration: ISRCTN43622374.REALITY was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development, the Wellcome Trust, and Medical Research Council (MRC) (grant number G1100693). Additional funding support was provided by the PENTA Foundation and core support to the MRC Clinical Trials Unit at University College London (grant numbers MC_UU_12023/23 and MC_UU_12023/26). Cipla Ltd, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for REALITY, and ready-to-use supplementary food was purchased from Valid International. A. J. P. is funded by the Wellcome Trust (grant number 108065/Z/15/Z). J. A. B. is funded by the JGHTS (grant number MR/M007367/1). The Malawi-Liverpool–Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine (grant number 101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi (grant number 203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust, United Kingdom. Permission to publish was granted by the Director of KEMRI. This supplement was supported by funds from the Bill & Melinda Gates Foundation

Clinical Implications of HIV Treatment and Prevention for Polygamous Families in Kenya and Uganda: "My Co-Wife Is the One Who Used to Encourage Me".

Polygamy is the practice of marriage to multiple partners. Approximately 6-11% of households in Uganda and 4-11% of households in Kenya are polygamous. The complex families produced by polygamous marriage customs give rise to additional considerations for healthcare providers and public health messaging around HIV care. Using 27 in-depth, semi-structured qualitative interviews with participants in two studies in rural Kenya and Uganda, we analysed challenges and opportunities that polygamous families presented in the diagnosis, treatment and prevention of HIV, and provider roles in improving HIV outcomes in these families. Overall, prevention methods seemed more justifiable to families where co-wives live far apart than when all members live in the same household. In treatment, diagnosis of one member did not always lead to disclosure to other members, creating an adverse home environment; but sometimes diagnosis of one wife led not only to diagnosis of the other, but also to greater household support

"I was still very young": agency, stigma and HIV care strategies at school, baseline results of a qualitative study among youth in rural Kenya and Uganda.

IntroductionAdolescents and young adults living with HIV (AYAH) have the lowest rates of retention in HIV care and antiretroviral therapy (ART) adherence, partly due to the demands of school associated with this life stage, to HIV-related stigma and to fears of serostatus disclosure. We explore the implications of school-based stigma and disclosure on the development of agency during a critical life stage in rural Kenya and Uganda.MethodsWe conducted a qualitative study in the baseline year of the SEARCH Youth study, a combination intervention using a life-stage approach among youth (15-24 years old) living with HIV in western Kenya and southwestern Uganda to improve viral load suppression and health outcomes. We conducted in-depth, semi-structured interviews in 2019 with three cohorts of purposively selected study participants (youth [n = 83], balanced for sex, life stage and HIV care status; recommended family members of youth [n = 33]; and providers [n = 20]). Inductive analysis exploring contextual factors affecting HIV care engagement revealed the high salience of schooling environments.ResultsStigma within school settings, elicited by non-consensual serostatus disclosure, medication schedules and clinic appointments, exerts a constraining factor around which AYAH must navigate to identify and pursue opportunities available to them as young people. HIV status can affect cross-generational support and cohort formation, as AYAH differ from non-AYAH peers because of care-related demands affecting schooling, exams and graduation. However, adolescents demonstrate a capacity to overcome anticipated stigma and protect themselves by selectively disclosing HIV status to trusted peers and caregivers, as they develop a sense of agency concomitant with this life stage. Older adolescents showed greater ability to seek out supportive relationships than younger ones who relied on adult caregivers to facilitate this support.ConclusionsSchool is a potential site of HIV stigma and also a setting for learning how to resist such stigma. School-going adolescents should be supported to identify helpful peers and selectively disclose serostatus as they master decision making about when and where to take medications, and who should know. Stigma is&nbsp;avoided&nbsp;by fewer visits to the clinic; providers should consider longer refills, discreet packaging and long-acting, injectable ART for students